In most outpatient centers the dialysate is prepared centrally such that the composition of the dialysate is the same for all patients. When delivered in this manner most patients tolerate the procedure well. However, there are patients who tolerate the procedure poorly, which has prompted a great deal of research focused on individualizing the composition of the dialysate in order to improve patient tolerability. Prescribing a patient-specific dialysate will become increasingly important as the age of and number of comorbid conditions increase in the dialysis population. Patients with end-stage renal disease (ESRD) depend on dialysis to maintain fluid and electrolyte balance. Hemodialysis allows for solutes to diffuse between blood and dialysate such that, over the course of the procedure, plasma composition is restored toward normal values. The makeup of the dialysate is of paramount importance in accomplishing this goal. In most out-patient settings patients receive hemodialysis using dialysate prepared in bulk and delivered via a central delivery system so that the composition of the dialysate is the same for all patients. While most patients tolerate the procedure when administered in this fashion, many patients suffer from hemodynamic instability or symptoms of dialysis disequilibrium. One strategy to improve the clinical tolerance to dialysis is to adjust the dialysate composition according to the individual characteristics of the patient. This article reviews recent developments on how the dialysate can be manipulated in order to improve patient tolerance. Individualizing the dialysate composition is likely to gain increasing importance given the advancing age and increasing number of comorbid conditions found in ESRD patients.